A crucial element in the development of effective therapeutic and prophylactic strategies for AIDS is an experimental animal model in which the course of immunodeficiency virus infection parallels the pathogenesis of the human disease. Simian immunodeficiency virus (SIV) infection of macaques satisfies this criterion and is therefore a relevant model. Notably, SIV induces an immunodeficiency syndrome in infected macaques that is remarkably similar in pathogenesis to human AIDS. An important use of this animal model system is the detailed study of pathogenesis and viral determinants of disease since many studies of this type are not feasible in humans. Such investigations should allow us to determine how primate lentiviruses destroy the immune system of their hosts, and this understanding should facilitate the development of more rational therapeutic antiviral strategies. The goals of this project include: 1) the molecular characterization of novel SIV's for phylogenetic studies and as reagents for pathogenesis and vaccine studies; and 2) delineation of the pathogenesis of SIV-induced AIDS.